Source-Separated Magnetic Susceptibility Reveals Postoperative Brain Changes in Newborns with Congenital Heart Disease

BACKGROUND AND PURPOSE: Congenital heart disease (CHD) is a significant risk factor for neurodevelopmental impairments, yet the underlying brain alterations in the early postnatal period remain poorly understood. This prospective study measured regional magnetic susceptibilities to characterize tissue composition changes in the brain of newborns with CHD. MATERIALS AND METHODS: A total of 51 newborns with CHD requiring cardiac surgery and 69 healthy controls were enrolled. Of these, 42 newborns with CHD and 65 healthy controls were included in the analysis, resulting in 29 preoperative MRI scans (postmenstrual age = 39.1 ± 1.2 weeks), 28 postoperative MRI scans (postmenstrual age = 43.0 ± 2.1 weeks), and 65 control scans (postmenstrual age = 42.8 ± 2.3 weeks). Quantitative susceptibility mapping (QSM) with source separation was performed to assess paramagnetic susceptibility and diamagnetic susceptibility. In a subset of the cohort, postoperative C-reactive protein levels were measured to assess systemic inflammation and Bayley-III test was performed at 18 months to evaluate neurodevelopment. RESULTS: Postoperative CHD scans demonstrated higher paramagnetic susceptibility in the thalamus and frontal lobe and higher diamagnetic susceptibility in the deep gray matter, lentiform nucleus, thalamus, and occipital lobe, compared with controls (all p < 0.05), whereas no differences were observed between preoperative CHD and control scans. Within the CHD group, single-ventricle physiology was associated with higher postoperative paramagnetic susceptibility and diamagnetic susceptibility compared with two-ventricle physiology (p < 0.05). In addition, postoperative paramagnetic susceptibility and diamagnetic susceptibility showed positive associations with postoperative C-reactive protein levels and negative associations with Bayley-III developmental scores at 18 months of age, particularly in receptive language and gross motor domains (p < 0.05). CONCLUSIONS: These findings suggest that susceptibility alterations emerge after cardiac surgery and are linked to poorer developmental outcomes. Source-separated QSM may serve as a sensitive biomarker of brain tissue alterations and neurodevelopmental risk in newborns with CHD.